Gut bacteria make neurotransmitters to shape the newborn immune system

Weill Cornell Medicine investigators discovered that unique bacteria colonize the gut shortly after birth and make the neurotransmitter serotonin to educate gut immune cells. This prevents allergic reactions to food and the bacteria themselves during early development.

The preclinical study, published in Science Immunology on Mar. 15, showed that bacteria abundant in the guts of newborns produce serotonin, which promotes the development of immune cells called T-regulatory cells or Tregs. These cells suppress inappropriate immune responses to help prevent autoimmune diseases and dangerous allergic reactions to harmless food items or beneficial gut microbes.

"The gut is now known as the second human brain as it makes over 90 percent of the neurotransmitters in the human body. While neurotransmitters such as serotonin are best known for their roles in brain health, receptors for neurotransmitters are located throughout the human body," explained the study's senior author, Dr. Melody Zeng, an assistant professor of immunology in the Gale and Ira Drukier Institute for Children's Research and the Department of Pediatrics at Weill Cornell Medicine.

Gut Bacteria in Babies Provide a Helping Hand

The researchers observed that the neonatal mouse gut had much higher levels of neurotransmitters, including serotonin, than the adult gut. "So far, almost all studies of gut neurotransmitters were conducted in adult animals or human subjects, where a specific gut cell type called enterochromaffin cells produce neurotransmitters," said Dr. Zeng. "However, we discovered that this isn't the case in the newborn gut where most of the serotonin is made by bacteria that are more abundant in the neonatal gut."

This was also confirmed in babies through a human infant stool biobank that the Zeng lab has established in collaboration with the Neonatal Intensive Care Unit in the NewYork-Presbyterian Alexandra Cohen Hospital for Women and Newborns. These samples were obtained with parental consent and deidentified.

The study results suggest that before the neonatal gut is mature enough to make its own neurotransmitters, unique gut bacteria may supply neurotransmitters that are needed for critical biological functions during early development.

"We found that gut bacteria in young mice not only directly produce serotonin but also decrease an enzyme called monoamine oxidase that normally breaks down serotonin, thus keeping gut serotonin levels high," said the study's lead author Dr. Katherine Sanidad, postdoctoral associate in pediatrics at Weill Cornell Medicine.

The high serotonin levels shift the balance of immune cells by increasing the number of Tregs, which helps prevent the immune system from overreacting and attacking gut bacteria or food antigens. "The neonatal gut needs these serotonin-producing bacteria to keep the immune system in check," Dr. Sanidad added.

Healthy Immune System Helps Later in Life

Dr. Zeng noted that this work underscores the importance of having the right types of beneficial bacteria soon after birth. Babies in developed countries have better access to antibiotics, less exposure to diverse microbes in their clean environments and potentially unhealthy diets that may significantly impact the abundance of serotonin-producing bacteria in their intestines.

As a result, these babies may have fewer Tregs and develop immune reactions to their own gut bacteria, or allergies to food. This may be one reason food allergies have become increasingly common in children, particularly in developed countries. "If educated properly, the immune system in babies would recognize that things like peanuts and eggs are okay, and it doesn't have to attack them," she said. This may also have an impact on developing autoimmune diseases -- when the immune system attacks the body's own healthy cells -- later in life.

The team next plans to look at bacteria in human infant stool samples to measure their production of serotonin, other neurotransmitters and molecules that may help train the immune system to prevent future immune-related diseases, such as allergies, infections and cancer.

"It's essential to understand how the immune system is trained during early life, but this is understudied in newborns and children. Further studies of these developmental periods may hopefully lead us to mitigation approaches to reduce the risk of inflammatory diseases like food allergies and inflammatory bowel disease later in life," Dr. Sanidad said.

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First-ever sighting of a live newborn great white

Great whites, the largest predatory sharks in the world with the most fatal attacks on humans, are tough to imagine as newborn babies. That is partially because no one has seen one in the wild, it seems, until now.

Wildlife filmmaker Carlos Gauna and UC Riverside biology doctoral student Phillip Sternes were scanning the waters for sharks on July 9, 2023, near Santa Barbara on California's central coast.

That day, something exciting appeared on the viewfinder of Gauna's drone camera.

It was a shark pup unlike any they'd ever seen.

Great whites, referred to only as white sharks by scientists, are gray on top and white on the bottom.

But this roughly 5-foot-long shark was pure white.

"We enlarged the images, put them in slow motion, and realized the white layer was being shed from the body as it was swimming," Sternes said.

"I believe it was a newborn white shark shedding its embryonic layer."

These observations are documented in a new paper in the Environmental Biology of Fishes journal.

The paper also details the significance of having seen a live newborn white shark.

Gauna is known online as The Malibu Artist. He has spent thousands of hours filming sharks around the world, and his videos of them swimming close to beachgoers have millions of views.

What he and Sternes observed could help solve the longstanding mystery of great white birthing habits.

"Where white sharks give birth is one of the holy grails of shark science. No one has ever been able to pinpoint where they are born, nor has anyone seen a newborn baby shark alive," Gauna said.

"There have been dead white sharks found inside deceased pregnant mothers. But nothing like this."

Though the paper authors acknowledge it is possible the white film the shark shed could have been a skin condition, the duo do not believe this to be the case.

"If that is what we saw, then that too is monumental because no such condition has ever been reported for these sharks," Gauna said.

For many reasons, the duo believes what they saw was in fact a newborn great white.

First, great white females give birth to live pups. While in utero, the embryonic sharks might feed on unfertilized eggs for protein.

The mothers offer additional nourishment to the growing shark pups with a 'milk' secreted in the uterus.

"I believe what we saw was the baby shedding the intrauterine milk," Sternes said.

A second reason is the presence of large, likely pregnant great whites in this location.

Gauna had observed them here in previous years, and in the weeks leading up to the observation.

"I filmed three very large sharks that appeared pregnant at this specific location in the days prior. On this day, one of them dove down, and not long afterwards, this fully white shark appears," Gauna said.

"It's not a stretch to deduce where the baby came from."

Thirdly, the shark's size and shape are also indicative of a newborn.

What the two observed was thin, short, and rounded. "In my opinion, this one was likely hours, maybe one day old at most," Sternes said.

Finally, this location off the coast of central California has long been proposed as a birthing location for great whites.

"There are a lot of hypothetical areas, but despite intense interest in these sharks, no one's seen a birth or a newborn pup in the wild," Sternes said.

"This may well be the first evidence we have of a pup in the wild, making this a definitive birthing location."

Many scholars believe great whites are born farther out at sea.

That this pup was filmed so close to shore -- roughly 1,000 feet from the beach -- is significant because its age means it was likely born in shallow waters.

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Exposure to air pollution while in the womb is linked to adverse changes in cell processes in new-born babies

Exposure to air pollution while in the womb is linked to alterations in proteins that can be detected after a baby is born, and which affect cell processes such as autophagy, the "self-eating" of damaged cells that occurs in response to stress.

Dr Olga Gorlanova, a research physician at the University Children's Hospital, University of Basel, Switzerland, told the European Respiratory Society International Congress in Milan, Italy, that her study also showed that healthy, new-born babies had individual and different responses to their mothers' exposure to air pollution during pregnancy. This might mean that some babies were more vulnerable to it than others. This was the case even if they were born into households in areas with relatively low levels of pollution.

Earlier work by Dr Gorlanova and her colleagues had shown that exposure to air pollution during pregnancy could affect lung function and the immune system in new-borns. In the current study, they looked at proteins involved in autophagy, ageing and cell remodelling to see how prenatal exposure to air pollution could affect them.

The researchers measured 11 proteins found in the cord blood of 449 healthy new-born babies from the Bern Basel Infant Lung Development (BILD) cohort study. The BILD study, started in 1999 in Bern, aims to recruit 1000 babies by 2025. It is investigating the effects of genetics and the environment (particularly air pollution) on lung development in babies and children.

Dr Gorlanova and colleagues measured the mothers' exposure to nitrogen dioxide (NO2) and tiny particles called PM10,which areparticulate matter measuring 10 microns or less in diameter. Vehicle emissions, tyre and brake wear, and smoke are some of the sources of these pollutants. They found that NO2 and PM10 were both linked to changes in proteins involved in autophagy. Exposure to NO2 was linked to a decrease in the activity of the proteins SIRT1 and IL-8, and an increase in levels of the Beclin-1 protein.

"Our results indicate that NO2, a pollutant formed mainly from traffic emissions, is associated with increased levels of Beclin-1 protein, which is central to initiating autophagy. Exposure to higher NO2 was also linked to decreased levels of SIRT1, which is a protein that plays a protective role in stress resistance, inflammation and aging. IL-8 is a protein active in certain inflammatory cells," said Dr Gorlanova.

"We grouped the babies into four distinct clusters according to the levels of air pollution they were exposed to while in the womb. The four clusters all had similar concentrations of the proteins being studied but had differences their exposure to NO2 and PM10 air pollution. One cluster had low concentrations of nine proteins, while another cluster, consisting of seven percent of all the babies, had higher levels of proteins that are involved in inflammatory and remodelling processes: IL-8 and IL-1B. Both these groups of new-borns had been exposed to lower, although differing, levels of prenatal air pollution than the other two groups. Our findings suggest that healthy new-borns have an individual response pattern to air pollution. We think that this may be an indication that some babies are more vulnerable to it than others.

"Additionally, our work adds to the growing body of evidence that autophagy-related mechanisms may be involved in how human cells react to air pollution. The findings are consistent with evidence from tissue and animal research. Further exploration of these mechanisms may help to better understand the deleterious effects of pollution on infants."

The researchers plan to examine whether babies with distinct protein response patterns to air pollution will suffer from more breathing problems during infancy and childhood compared to those that do not show the same protein responses.

Professor Marielle Pijnenburg, associate professor of pediatric pulmonology and head of the Department of Pediatric Respiratory Medicine and Allergology at Erasmus Medical Center, Rotterdam, The Netherlands, is head of the ERS group on paediatrics and was not involved with the research. She commented: "This study adds to the growing body of evidence that air pollution can affect the health of children before and after they are born. It contributes to other research showing that autophagy-related mechanisms may be involved in how human cells react to air pollution. We need to know more about how these mechanisms can affect the health of lungs, and we need to understand why some new-borns seem to be more susceptible to air pollution than others.

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Newborns’ brains already organized into functional networks

Right from birth, human brains are organized into networks that support mental functions such as vision and attention, a new study shows.

Previous studies had shown that adults have seven such functional networks in the brain. This study, the first to take a fine-grained, whole-brain approach in newborns, found five of those networks are operating at birth.

Crucially, the study also found individual variability in those networks in newborns, which may have implications for how genetics affects behavior in adults.

"For centuries, humans have wondered about what makes them unique and the role of genetic programming versus our lifetime of experience," said Zeynep Saygin, senior author of the study and assistant professor of psychology at The Ohio State University.

"Our study shows variability in the brain at birth that may be related to some of the behavioral differences we see in adults."

The study, published recently in the journal NeuroImage, was led by M. Fiona Molloy, a psychology graduate student at Ohio State.

The researchers analyzed fMRI scans of the brains of 267 newborns, most less than a week old, who were part of the Developing Human Connectome Project. All infants were scanned for 15 minutes while they were asleep.

The study involved analysis of the smallest bits of brain possible with MRI -- called voxels or volumetric pixels -- to see how the signals of each voxel were related to other voxels in the brain.

"Even when we're sleeping, the brain is active and different parts are communicating with each other," Saygin said.

"We identify networks by finding which parts of the brain show similar patterns of activity at the same time -- for example when one area activates, the other does too. They are talking to each other."

Findings showed five networks in newborns that resembled those found in adults: the visual, default, sensorimotor, ventral attention and high-level vision networks.

Adults have two additional networks not found in the brains of newborns: the control and limbic networks. These are both involved with higher-level functions, Saygin explained.

The control network allows adults to make plans to meet goals. The limbic network is involved in emotional regulation.

"Babies have little cognitive control and emotional regulation, so it is not surprising that these networks aren't developed," Saygin said.

"But one possibility would have been that they are set up at birth and just need to be honed. That's not what we found, though. Those networks are not there at all yet and must develop through experience."

The researchers also examined individual differences in the brain networks of the newborns studied. Results showed that the ventral attention network showed the most variability in the newborns. This is the network involved in directing attention to important stimuli encountered in the world, especially something that may be unexpected.

"Our results suggest that the ventral attention network is a stable source of individual variability that exists at birth and perhaps persists through the lifetime," she said.

In adults, this individual variability in network organization has been linked to behavior and different disorders.

"We see individual differences in network organization as early as birth, and it could be interesting to see if these differences predict behavior or risk of psychological disorders later in life," Molloy said.

In another analysis, the researchers used tissue samples of human brains available through the Allan Human Brain Atlas to explore how differences in the brain networks in the newborns may be tied to differences in gene expression -- the process of turning on or activating genes.

They found multiple genes from the brain tissue samples that may have led to the specific brain organizations they found in individual newborns in the study.

"This might uncover a potential genetic basis for why we're seeing these differences in the networks of newborns in our study," she said.

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Forest fires linked to low birth weight in newborns

Women exposed to smoke from landscape fires during pregnancy are more likely to give birth to babies with low or very low birth weights, according to findings published in eLife.

The study is the first to report a link between low birth weight and exposure to fire smoke in low and middle-income countries (LMICs), where 90% of low birth weight infants are born and landscape fires are prevalent.

Landscape fires, such as wildfires, tropical deforestation fires and agricultural biomass burning, play an important role in maintaining terrestrial ecosystems. Yet, landscape fire smoke is triggering a costly and growing global public health problem, causing recurrent episodes of pollution mostly affecting LMICs.

Previous studies have shown that exposure to fire smoke during pregnancy is linked to low birth weight, which itself is a public health problem in LMICs. Reducing the risk of low birth weight is one of the World Health Organization's global targets for 2025.

"Babies with low birth weights are at higher risk of a range of diseases in later life compared to normal weight newborns," explains co-first author Jiajianghui Li, a PhD student at the Institute of Reproductive and Child Health, School of Public Health Science Centre, Peking University, China. "Several studies have shown the effects of landscape fire smoke on acute lung and heart conditions, but the health impacts of these pollutants on susceptible pregnant women are not well known. We wanted to explore the association between birth weight and exposure to fire source pollution across several countries and over a long time period."

The researchers conducted a case-control study in 54 LMICs where they matched 108,137 groups of siblings to their mothers. They used surveys conducted by the US Agency for International Development between 2000 and 2014 to find out information about sibling birth weights and other health and demographic factors. They then assessed exposure to landscape fire pollutants using data on fire emissions from the Global Fire Emission Database and a model that converted this data into ground-surface concentrations of particulate matter in different regions.

Their analysis showed that an increase in exposure of one microgram per cubic metre of fire-sourced particulate matter was associated with a 2.17-gram reduction in birth weight. "The effect was even more pronounced when we looked at whether exposure to fire smoke was linked to low or very low birth weight; for every microgram per cubic metre increase in particulate matter exposure, the risks of low and very low birth weight increased by around three and 12 per cent, respectively," says co-first author Tianjia Guan, an assistant professor at the Department of Health Policy, School of Health Policy and Management, Chinese Academy of Medical Sciences and Peking Union Medical College, China.

The researchers found that very low birth weight was most strongly linked to the pollution. To find out why, they developed a model that looked at the average birth weight of infants within single families. Newborns in families that had lower birth weights on average were more susceptible to the risks of fire smoke pollution than those who had moderate baseline birthweights. "This suggests that other factors affecting maternal and foetal health, such as nutrition or maternal employment status, might make mothers and their developing infants even more susceptible to the risks of pollution," says co-first author Qian Guo, a PhD student at the School of Energy and Environmental Engineering, University of Science and Technology, China.

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New mothers’ sleep loss linked to accelerated aging

When new mothers complain that all those sleepless nights caring for their newborns are taking years off their life, they just might be right, UCLA research published this summer in the journal Sleep Health suggests.

Scientists studied 33 mothers during their pregnancies and the first year of their babies' lives, analyzing the women's DNA from blood samples to determine their "biological age," which can differ from chronological age. They found that a year after giving birth, the biological age of mothers who slept less than seven hours a night at the six-month mark was three to seven years older than those who logged seven hours or more.

Mothers who slept less than seven hours also had shorter telomeres in their white blood cells. These small pieces of DNA at the ends of chromosomes act as protective caps, like the plastic tips on the ends of shoelaces. Shortened telomeres have been linked to a higher risk of cancers, cardiovascular and other diseases, and earlier death.

"The early months of postpartum sleep deprivation could have a lasting effect on physical health," said the study's first author, Judith Carroll, UCLA's George F. Solomon Professor of Psychobiology. "We know from a large body of research that sleeping less than seven hours a night is detrimental to health and increases the risk of age-related diseases."

While participants' nightly sleep ranged from five to nine hours, more than half were getting less than seven hours, both six months and one year after giving birth, the researchers report.

"We found that with every hour of additional sleep, the mother's biological age was younger," said Carroll, a member of the Cousins Center for Psychoneuroimmunology at UCLA's Jane and Terry Semel Institute for Neuroscience and Human Behavior. "I, and many other sleep scientists, consider sleep health to be just as vital to overall health as diet and exercise."

Carroll urged new mothers take advantage of opportunities to get a little extra sleep, like taking naps during the day when their baby is asleep, accepting offers of assistance from family and friends, and, when possible, asking their partner to help with the baby during the night or early morning. "Taking care of your sleep needs will help you and your baby in the long run," she said.

Co-author Christine Dunkel Schetter, a distinguished professor of psychology and psychiatry at UCLA, said the study results "and other findings on maternal postpartum mental health provide impetus for better supporting mothers of young infants so that they can get sufficient sleep -- possibly through parental leave so that both parents can bear some of the burden of care, and through programs for families and fathers."

Dunkel Schetter added that while accelerated biological aging linked to sleep loss may increase women's health risks, it doesn't automatically cause harm to their bodies. "We don't want the message to be that mothers are permanently damaged by infant care and loss of sleep," she emphasized. "We don't know if these effects are long lasting."

'This aisle is closed': Using epigenetics to determine biological age

The study used the latest scientific methods of analyzing changes in DNA to assess biological aging -- also known as epigenetic aging, Dunkel Schetter said. DNA provides the code for making proteins, which carry out many functions in the cells of our body, and epigenetics focuses on whether regions of this code are "open" or "closed."

"You can think of DNA as a grocery store," Carroll said, "with lots of basic ingredients to build a meal. If there is a spill in one aisle, it may be closed, and you can't get an item from that aisle, which might prevent you from making a recipe. When access to DNA code is 'closed,' then those genes that code for specific proteins cannot be expressed and are therefore turned off."

Because specific sites within DNA are turned on or off with aging, the process acts as a sort of clock, Carroll said, allowing scientists to estimate individuals' biological age. The greater an individual's biological, or epigenetic, age, the greater their risk of disease and earlier death.

The study's cohort -- which included women who ranged in age from 23 to 45 six months after giving birth -- is not a large representative sample of women, the authors said, and more studies are needed to better understand the long-term impact of sleep loss on new mothers, what other factors might contribute to sleep loss and whether the biological aging effects are permanent or reversible.

Carroll and Dunkel Schetter reported last year that a mother's stress prior to giving birth may accelerate her child's biological aging, which is a form of "intergenerational transfer of health risk," Dunkel Schetter said.

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